UniProtKB - P08543 (RIR1_HHV11)
Protein
Ribonucleoside-diphosphate reductase large subunit
Gene
RIR1
Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Functioni
Ribonucleoside-diphosphate reductase holoenzyme provides the precursors necessary for viral DNA synthesis. Allows virus growth in non-dividing cells, as well as reactivation from latency in infected hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides (By similarity). Prevents necroptosis by targeting host RIPK1 and RIPK3 thereby preventing the formation of necroptotic RIPK1-RIPK3 complexes (PubMed:25674983, PubMed:30050136). In addition, inhibits extrinsic apoptosis by targeting host CASP8 (PubMed:25674983).UniRule annotation2 Publications
Catalytic activityi
- [thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-diphosphateUniRule annotationEC:1.17.4.1UniRule annotation
: DNA replication Pathwayi
This protein is involved in the pathway DNA replication, which is part of Genetic information processing.UniRule annotationView all proteins of this organism that are known to be involved in the pathway DNA replication and in Genetic information processing.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 566 | SubstrateUniRule annotation | 1 | |
Sitei | 582 | Important for hydrogen atom transferUniRule annotation | 1 | |
Binding sitei | 612 | Substrate; via amide nitrogenUniRule annotation | 1 | |
Active sitei | 791 | Proton acceptorUniRule annotation | 1 | |
Active sitei | 793 | Cysteine radical intermediateUniRule annotation | 1 | |
Active sitei | 795 | Proton acceptorUniRule annotation | 1 | |
Sitei | 808 | Important for hydrogen atom transferUniRule annotation | 1 | |
Sitei | 1111 | Important for electron transferUniRule annotation | 1 | |
Sitei | 1112 | Important for electron transferUniRule annotation | 1 | |
Sitei | 1132 | Interacts with thioredoxin/glutaredoxinUniRule annotation | 1 | |
Sitei | 1135 | Interacts with thioredoxin/glutaredoxinUniRule annotation | 1 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-UniRule
- ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Source: UniProtKB-UniRule
GO - Biological processi
- DNA replication Source: UniProtKB-UniRule
- release from viral latency Source: UniProtKB-KW
Keywordsi
Molecular function | Oxidoreductase |
Biological process | DNA replication, Host-virus interaction, Inhibition of host caspases by virus, Modulation of host cell apoptosis by virus, Viral latency, Viral reactivation from latency |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis |
UniPathwayi | UPA00326 |
Names & Taxonomyi
Protein namesi | Recommended name: Ribonucleoside-diphosphate reductase large subunitUniRule annotation (EC:1.17.4.1UniRule annotation)Short name: R1UniRule annotation Alternative name(s): Ribonucleotide reductase large subunitUniRule annotation |
Gene namesi | Name:RIR1UniRule annotation Synonyms:ICP61 Publication Ordered Locus Names:UL39 |
Organismi | Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) |
Taxonomic identifieri | 10299 [NCBI] |
Taxonomic lineagei | Viruses › Duplodnaviria › Heunggongvirae › Peploviricota › Herviviricetes › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 73 – 76 | VQCG → AAAA: Abolished interaction with human RIPK3. Loss of ability to prevent necroptosis. 3 Publications | 4 |
Chemistry databases
ChEMBLi | CHEMBL3840 |
DrugCentrali | P08543 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000187236 | 1 – 1137 | Ribonucleoside-diphosphate reductase large subunitAdd BLAST | 1137 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 582 ↔ 808 | Redox-activeUniRule annotation |
Keywords - PTMi
Disulfide bondProteomic databases
PRIDEi | P08543 |
Interactioni
Subunit structurei
Heterotetramer composed of a homodimer of the large subunit (R1) and a homodimer of the small subunit (R2) (By similarity). Larger multisubunit protein complex are also active, composed of (R1)n(R2)n (By similarity).
Interacts (via RIP homotypic interaction motif) with human RIPK3 (via RIP homotypic interaction motif) (PubMed:25316792, PubMed:25674983).
Interacts (via RIP homotypic interaction motif) with human RIPK1 (via RIP homotypic interaction motif) (PubMed:25674983).
Interacts (via C-terminus) with host CASP8 (PubMed:25674983).
UniRule annotation2 PublicationsProtein-protein interaction databases
BioGRIDi | 971405, 2 interactors |
DIPi | DIP-57653N |
IntActi | P08543, 5 interactors |
MINTi | P08543 |
Chemistry databases
BindingDBi | P08543 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 581 – 582 | Substrate bindingUniRule annotation | 2 | |
Regioni | 791 – 795 | Substrate bindingUniRule annotation | 5 | |
Regioni | 968 – 972 | Substrate bindingUniRule annotation | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 64 – 84 | RIP homotypic interaction motif (RHIM)1 PublicationAdd BLAST | 21 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 150 – 154 | Poly-Pro | 5 | |
Compositional biasi | 190 – 239 | Asp/Ser-richAdd BLAST | 50 |
Sequence similaritiesi
Belongs to the ribonucleoside diphosphate reductase large chain family.UniRule annotation
Family and domain databases
HAMAPi | MF_04026, HSV_RIR1, 1 hit |
InterProi | View protein in InterPro IPR034717, HSV_RIR1 IPR013346, NrdE_NrdA IPR000788, RNR_lg_C IPR013509, RNR_lsu_N IPR039718, Rrm1 |
PANTHERi | PTHR11573, PTHR11573, 1 hit |
Pfami | View protein in Pfam PF02867, Ribonuc_red_lgC, 1 hit PF00317, Ribonuc_red_lgN, 1 hit |
PRINTSi | PR01183, RIBORDTASEM1 |
TIGRFAMsi | TIGR02506, NrdE_NrdA, 1 hit |
PROSITEi | View protein in PROSITE PS00089, RIBORED_LARGE, 1 hit |
i Sequence
Sequence statusi: Complete.
P08543-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MASRPAASSP VEARAPVGGQ EAGGPSAATQ GEAAGAPLAH GHHVYCQRVN
60 70 80 90 100
GVMVLSDKTP GSASYRISDN NFVQCGSNCT MIIDGDVVRG RPQDPGAAAS
110 120 130 140 150
PAPFVAVTNI GAGSDGGTAV VAFGGTPRRS AGTSTGTQTA DVPTEALGGP
160 170 180 190 200
PPPPRFTLGG GCCSCRDTRR RSAVFGGEGD PVGPAEFVSD DRSSDSDSDD
210 220 230 240 250
SEDTDSETLS HASSDVSGGA TYDDALDSDS SSDDSLQIDG PVCRPWSNDT
260 270 280 290 300
APLDVCPGTP GPGADAGGPS AVDPHAPTPE AGAGLAADPA VARDDAEGLS
310 320 330 340 350
DPRPRLGTGT AYPVPLELTP ENAEAVARFL GDAVNREPAL MLEYFCRCAR
360 370 380 390 400
EETKRVPPRT FGSPPRLTED DFGLLNYALV EMQRLCLDVP PVPPNAYMPY
410 420 430 440 450
YLREYVTRLV NGFKPLVSRS ARLYRILGVL VHLRIRTREA SFEEWLRSKE
460 470 480 490 500
VALDFGLTER LREHEAQLVI LAQALDHYDC LIHSTPHTLV ERGLQSALKY
510 520 530 540 550
EEFYLKRFGG HYMESVFQMY TRIAGFLACR ATRGMRHIAL GREGSWWEMF
560 570 580 590 600
KFFFHRLYDH QIVPSTPAML NLGTRNYYTS SCYLVNPQAT TNKATLRAIT
610 620 630 640 650
SNVSAILARN GGIGLCVQAF NDSGPGTASV MPALKVLDSL VAAHNKESAR
660 670 680 690 700
PTGACVYLEP WHTDVRAVLR MKGVLAGEEA QRCDNIFSAL WMPDLFFKRL
710 720 730 740 750
IRHLDGEKNV TWTLFDRDTS MSLADFHGEE FEKLYQHLEV MGFGEQIPIQ
760 770 780 790 800
ELAYGIVRSA ATTGSPFVMF KDAVNRHYIY DTQGAAIAGS NLCTEIVHPA
810 820 830 840 850
SKRSSGVCNL GSVNLARCVS RQTFDFGRLR DAVQACVLMV NIMIDSTLQP
860 870 880 890 900
TPQCTRGNDN LRSMGIGMQG LHTACLKLGL DLESAEFQDL NKHIAEVMLL
910 920 930 940 950
SAMKTSNALC VRGARPFNHF KRSMYRAGRF HWERFPDARP RYEGEWEMLR
960 970 980 990 1000
QSMMKHGLRN SQFVALMPTA ASAQISDVSE GFAPLFTNLF SKVTRDGETL
1010 1020 1030 1040 1050
RPNTLLLKEL ERTFSGKRLL EVMDSLDAKQ WSVAQALPCL EPTHPLRRFK
1060 1070 1080 1090 1100
TAFDYDQKLL IDLCADRAPY VDHSQSMTLY VTEKADGTLP ASTLVRLLVH
1110 1120 1130
AYKRGLKTGM YYCKVRKATN SGVFGGDDNI VCMSCAL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1034 | A → P in AAA45805 (PubMed:2835765).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 70 | N → S in strain: Nonneuroinvasive mutant HF10, 17 syn+ and Isolate pYN1. | 1 | |
Natural varianti | 1133 | M → T in strain: Nonneuroinvasive mutant HF10. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X14112 Genomic DNA Translation: CAA32314.1 M18410 Genomic DNA Translation: AAA45805.1 DQ889502 Genomic DNA Translation: ABI63501.1 FJ593289 Genomic DNA Translation: ACM62262.1 |
PIRi | A26536, WMBEB1 |
RefSeqi | YP_009137114.1, NC_001806.2 |
Genome annotation databases
GeneIDi | 2703361 |
KEGGi | vg:2703361 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X14112 Genomic DNA Translation: CAA32314.1 M18410 Genomic DNA Translation: AAA45805.1 DQ889502 Genomic DNA Translation: ABI63501.1 FJ593289 Genomic DNA Translation: ACM62262.1 |
PIRi | A26536, WMBEB1 |
RefSeqi | YP_009137114.1, NC_001806.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 971405, 2 interactors |
DIPi | DIP-57653N |
IntActi | P08543, 5 interactors |
MINTi | P08543 |
Chemistry databases
BindingDBi | P08543 |
ChEMBLi | CHEMBL3840 |
DrugCentrali | P08543 |
Proteomic databases
PRIDEi | P08543 |
Genome annotation databases
GeneIDi | 2703361 |
KEGGi | vg:2703361 |
Enzyme and pathway databases
UniPathwayi | UPA00326 |
Reactomei | R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis |
Family and domain databases
HAMAPi | MF_04026, HSV_RIR1, 1 hit |
InterProi | View protein in InterPro IPR034717, HSV_RIR1 IPR013346, NrdE_NrdA IPR000788, RNR_lg_C IPR013509, RNR_lsu_N IPR039718, Rrm1 |
PANTHERi | PTHR11573, PTHR11573, 1 hit |
Pfami | View protein in Pfam PF02867, Ribonuc_red_lgC, 1 hit PF00317, Ribonuc_red_lgN, 1 hit |
PRINTSi | PR01183, RIBORDTASEM1 |
TIGRFAMsi | TIGR02506, NrdE_NrdA, 1 hit |
PROSITEi | View protein in PROSITE PS00089, RIBORED_LARGE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RIR1_HHV11 | |
Accessioni | P08543Primary (citable) accession number: P08543 Secondary accession number(s): B9VQG7, Q09I94 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | July 1, 1989 | |
Last modified: | February 10, 2021 | |
This is version 125 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families